Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management

Amirifar, Parisa; Ranjouri, Mohammad Reza; Lavin, Martin F.; Abolhassani, Hassan; Yazdani, Reza; Aghamohammadi, Asghar

doi:10.1080/1744666x.2020.1810570

Cited by 49 publications

(47 citation statements)

References 139 publications

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“…Respiratory tract infections and chronic lung disease are an important cause of morbidity and mortality in A-T [ 1 , 2 , 3 , 4 , 8 ]. However, the etiology and pathogenesis of the chronic pulmonary disorders in these patients have not been well studied.…”

Section: Discussionmentioning

confidence: 99%

“…However, the etiology and pathogenesis of the chronic pulmonary disorders in these patients have not been well studied. Recurrent aspiration and poor pulmonary clearance due to abnormal muscle tone as well as an abnormal immune response could contribute to lung complications, due not only to an increased susceptibility to infections but also to a chronically heightened inflammatory state [ 1 , 2 , 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of unrepaired DNA in ATM -deficient cells activates pathways causing the induction of type 1 IFNs, which lead to the inflammatory phenotype associated with A-T [ 1 ]. Other authors have hypothesized that ATM -deficient innate immune cells present an extended life due to altered DNA damage response, and could contribute to chronic inflammation, leading to the development of lung disease [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Ataxia-telangiectasia (A-T) is an autosomal recessive, multiorgan disease characterized by progressive cerebellar ataxia, ocular telangiectasia, and variable defects in both humoral and cell-mediated immunity, with predisposition to infections and cancer [ 1 , 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recurrent respiratory infections can result in progressive bronchiectasis and chronic lung disease [ 1 , 2 , 3 , 4 ]. Despite immunoglobulin replacement therapy (IRT) and/or antibiotic prophylaxis, recurrent infections are still one of the leading causes of morbidity and mortality in patients with A-T [ 1 , 3 ]. In addition, there is evidence of both inappropriate activations of the innate immune response and increased levels of pro-inflammatory cytokines in these patients, which could also influence the development of chronic lung disease [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

Méndez-Echevarría

Caminoa

Rabes

et al. 2021

Viruses

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Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied. Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses’ polymerase chain reaction were collected monthly, and between visits in case of symptoms. Results: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls (p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls (p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points (p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts (p < 0.05), particularly when these episodes were moderate/severe. Conclusions: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

Méndez-Echevarría

Caminoa

Rabes

et al. 2021

Viruses

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Combined Immunodeficiencies

Rubin,

Williams,

Lawrence

2024

Manual of Molecular and Clinical Laboratory Immunology

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Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi‐based consensus survey of international experts

et al. 2023

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Background/Objectives Ataxia telangiectasia (A‐T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A‐T. We aimed to understand the current international practice regarding cancer surveillance in A‐T and agreed‐upon approaches to develop cancer surveillance in A‐T. Design/Methods We used a consensus development method, the e‐Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A‐T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre‐specified consensus threshold was ≥75% agreement. Results Thirty‐five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence‐based guidelines are needed for cancer surveillance in people with A‐T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. Conclusion The international expert consensus statement confirms the need for evidence‐based cancer surveillance guidelines in A‐T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

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Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management

Cited by 49 publications

References 139 publications

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

Combined Immunodeficiencies

Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi‐based consensus survey of international experts

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